The proposed research is concerned with the mechanism by which chemical and physical carcinogens induced malignancy in vitro. In particular, it is proposed to investigate: (1) The cell cycle specificity for malignant transformation of two groups of carcinogen; those producing X-ray type damage, and those producing UV-type damage. In the first group will be X-irradiation and N-methyl-N'-nitro-N-nitrosoguanidine, and in the second group UV light and N-acetoxyacetylaminofluorene. (2) The potential of certain clinically useful drugs, which appear to inhibit DNA repair, to modify the carcinogenic response to the above carcinogens. It is proposed to study the effects of actinomycin D, caffeine, chloroquine and adriamycin. (3) The biochemical mechanism of action of the compounds listed in (2) above. (4) Activity of natural and synthetic retinoids in inhibiting malignant transformation.